Reactome | UniProt:P25963 NFKBIA

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UniProt:P25963 NFKBIA Show undefined attributes

chain	chain:1-317
checksum	088B313226786395
comment	FUNCTION Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:7479976, PubMed:36651806). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7796813, PubMed:7628694, PubMed:7878466, PubMed:7479976).SUBUNIT Interacts with RELA; the interaction requires the nuclear import signal (PubMed:1493333). Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (PubMed:9751059). Interacts with NKIRAS1 and NKIRAS2 (PubMed:10657303). Interacts with isoform 1 and isoform 2 of RWDD3; the interaction enhances sumoylation (PubMed:17956732, PubMed:23469069). Interacts with PRMT2 (PubMed:16648481). Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen (PubMed:20356841). Interacts with MEFV (PubMed:18577712). Interacts with DDRGK1; positively regulates NFKBIA phosphorylation and degradation (PubMed:23675531).SUBUNIT (Microbial infection) Interacts with HBV protein X.INTERACTION Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.INDUCTION Induced in adherent monocytes.PTM Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK and IKKB/IKBKB; disables inhibition of NF-kappa-B DNA-binding activity (PubMed:7796813, PubMed:7628694, PubMed:7878466, PubMed:8631829, PubMed:9701247, PubMed:10329681, PubMed:10882136). Phosphorylation at positions 32 and 36 is prerequisite to recognition by the SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and subsequent degradation (PubMed:7628694, PubMed:8631829, PubMed:9701247, PubMed:10329681). Phosphorylated at Ser-32 in response to FK506 treatment: phosphorylation is independent of IKKA/CHUK and IKKB/IKBKB and promotes NFKBIA degradation, followed by NF-kappa-B activation (PubMed:10574930). Phosphorylated at Tyr-42: its effect is however unclear (PubMed:8797825, PubMed:8940099). According to a report, phosphorylation at Tyr-42 activates NF-kappa-B without triggering proteolytic degradation of NFKBIA (PubMed:8797825). According to another publication, phosphorylation at Tyr-42 inhibits NF-kappa-B activity by preventing phosphorylation at Ser-32 and Ser-36 and subsequent ubiquitination and degradation (PubMed:8940099).PTM Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:7479976, PubMed:8631829, PubMed:9701247, PubMed:10329681, PubMed:20347421). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (PubMed:7479976, PubMed:10329681, PubMed:20347421). Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (PubMed:10437795, PubMed:20347421). The resulting polyubiquitination leads to protein degradation (PubMed:7628694, PubMed:7479976, PubMed:20347421). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (PubMed:10644755). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (PubMed:36651806).PTM Sumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome-mediated degradation of the protein thereby increasing the protein stability.PTM Hydroxylated by HIF1AN.PTM (Microbial infection) Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the NF-kappa-B inhibitor family.ONLINE INFORMATION NFKBIA mutation db
crossReference	[DatabaseIdentifier:10974420] Pharos - Targets:P25963 [DatabaseIdentifier:11070897] OpenTargets:ENSG00000100906 [DatabaseIdentifier:11621209] RefSeq:NP_065390.1 [DatabaseIdentifier:11725006] PDB:1IKN [DatabaseIdentifier:11725007] PDB:1NFI [DatabaseIdentifier:11725019] PDB:6TTU [DatabaseIdentifier:11725032] PDB:6Y1J [DatabaseIdentifier:11828260] PRO:P25963 [DatabaseIdentifier:11848904] GeneCards:P25963 [DatabaseIdentifier:11854106] ZINC - Substances:IKBA_HUMAN [DatabaseIdentifier:11861947] ZINC - Predictions - Purchasable:IKBA_HUMAN [DatabaseIdentifier:11864951] ZINC target:P25963 [DatabaseIdentifier:11884069] Orphanet:17400 [DatabaseIdentifier:11897438] HPA:ENSG00000100906-NFKBIA [DatabaseIdentifier:12107394] Ensembl:ENSP00000216797 [DatabaseIdentifier:12107395] Ensembl:ENST00000216797 [DatabaseIdentifier:12107396] Ensembl:ENSG00000100906
databaseName	UniProt
dbId	57208
description	recommendedName: NF-kappa-B inhibitor alpha alternativeName: I-kappa-B-alpha shortName: IkB-alpha shortName: IkappaBalpha alternativeName: Major histocompatibility complex enhancer-binding protein MAD3
displayName	UniProt:P25963 NFKBIA
geneName	NFKBIA IKBA MAD3 NFKBI
identifier	P25963
isSequenceChanged	false
keyword	3D-structure ANK repeat Cytoplasm Disease variant Ectodermal dysplasia Host-virus interaction Hydroxylation Isopeptide bond Nucleus Phosphoprotein Reference proteome Repeat Ubl conjugation
modified	[InstanceEdit:12187927] Wright, Adam, 2024-03-12
name	NFKBIA
otherIdentifier	11744000_a_at 11745878_x_at 11757894_x_at 1461_at 16791991 201502_PM_s_at 201502_s_at 3561040 3561041 3561043 3561044 3561046 3561048 3561050 3561053 3561054 4792 7978644 A_23_P106002 GE82547 GO:0002376 GO:0005515 GO:0005634 GO:0005654 GO:0005737 GO:0005829 GO:0005886 GO:0006351 GO:0006355 GO:0006606 GO:0006886 GO:0006913 GO:0006915 GO:0006954 GO:0007219 GO:0007249 GO:0007253 GO:0008139 GO:0010468 GO:0010745 GO:0010875 GO:0010888 GO:0012501 GO:0019899 GO:0023052 GO:0030154 GO:0031625 GO:0031663 GO:0032088 GO:0032495 GO:0032496 GO:0033209 GO:0033256 GO:0034142 GO:0035994 GO:0038061 GO:0042127 GO:0042802 GO:0043124 GO:0043226 GO:0043330 GO:0045638 GO:0045746 GO:0045893 GO:0045944 GO:0048856 GO:0050729 GO:0050853 GO:0051059 GO:0051247 GO:0060261 GO:0070417 GO:0070427 GO:0070431 GO:0070498 GO:0071356 GO:0098542 GO:0140311 GO:0140313 HMNXSV003036480 Hs.81328.0.S1_3p_a_at M69043_at PH_hs_0004662 TC14001036.hg
physicalEntity	[EntityWithAccessionedSequence:R-HSA-6782960] PolyUb-NFKBIA [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-168151] NFKBIA [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-177677] p-S32,S36-NFKBIA [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1168581] Ub-K21,22-p-S32,S36-NFKBIA [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-4656929] NFKBIA [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-4656935] monoSUMO1-K21-NFKBIA [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5228846] NFKBIA S32I [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9630119] NFKBIA F2_M37del [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5228805] NFKBIA M37K [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990180] ENSEMBL:ENSG00000100906 NFKBIA [ReferenceDNASequence:11028244] KEGG Gene (Homo sapiens):4792 NFKBIA [ReferenceDNASequence:11270412] NCBI Gene:4792 NFKBIA [ReferenceDNASequence:11270413] BioGPS Gene:4792 NFKBIA [ReferenceDNASequence:11270414] CTD Gene:4792 NFKBIA [ReferenceDNASequence:11270415] dbSNP Gene:4792 NFKBIA [ReferenceDNASequence:11270416] Monarch:4792 NFKBIA [ReferenceDNASequence:11348026] ENSEMBL_homo_sapiens_GENE:ENSG00000100906.12 NFKBIA [ReferenceDNASequence:11517665] UCSC:P25963 NFKBIA [ReferenceDNASequence:11802719] OMIM:164008 NFKBIA [ReferenceDNASequence:11876258] HGNC:7797 NFKBIA [ReferenceDNASequence:12198620] COSMIC (genes):NFKBIA NFKBIA
referenceTranscript	[ReferenceRNASequence:11447011] RefSeq:NM_020529.2 NFKBIA
schemaClass	ReferenceGeneProduct
secondaryIdentifier	IKBA_HUMAN B2R8L6
sequenceLength	317
species	[Species:48887] Homo sapiens
url	https://purl.uniprot.org/uniprot/P25963

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-6782960] PolyUb-NFKBIA [cytosol] [EntityWithAccessionedSequence:R-HSA-168151] NFKBIA [cytosol] [EntityWithAccessionedSequence:R-HSA-177677] p-S32,S36-NFKBIA [cytosol] [EntityWithAccessionedSequence:R-HSA-1168581] Ub-K21,22-p-S32,S36-NFKBIA [cytosol] [EntityWithAccessionedSequence:R-HSA-4656929] NFKBIA [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-4656935] monoSUMO1-K21-NFKBIA [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-5228846] NFKBIA S32I [cytosol] [EntityWithAccessionedSequence:R-HSA-9630119] NFKBIA F2_M37del [cytosol] [EntityWithAccessionedSequence:R-HSA-5228805] NFKBIA M37K [cytosol]
(referenceSequence)	[GroupModifiedResidue:6782990] ubiquitinylated lysine (PolyUb [cytosol]) at unknown position [ModifiedResidue:177659] O-phospho-L-serine at 32 [ModifiedResidue:203804] O-phospho-L-serine at 36 [GroupModifiedResidue:1168566] ubiquitinylated lysine (K48polyUb [cytosol]) at 21 [ModifiedResidue:203803] O-phospho-L-serine at 32 [GroupModifiedResidue:1168569] ubiquitinylated lysine (K48polyUb [cytosol]) at 22 [GroupModifiedResidue:4656996] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 21 [ReplacedResidue:5228852] L-serine 32 replaced with L-isoleucine [FragmentDeletionModification:5228817] Deletion of residues 1 to 36 [ReplacedResidue:5228849] L-methionine 37 replaced with L-lysine
(interactor)	[UndirectedInteraction:12284313] UniProt:P25963 <-> UniProt:P25799-1 (IntAct) [UndirectedInteraction:12284311] UniProt:P25963 <-> UniProt:Q9E7P0 (IntAct) [UndirectedInteraction:12284307] UniProt:P25963 <-> UniProt:P14340-PRO_0000037965 (IntAct) [UndirectedInteraction:12284305] UniProt:P25963 <-> UniProt:P14340 (IntAct) [UndirectedInteraction:12284301] UniProt:P25963 <-> UniProt:P56279 (IntAct) [UndirectedInteraction:12284299] UniProt:P25963 <-> UniProt:Q9H0I2 (IntAct) [UndirectedInteraction:12284297] UniProt:P25963 <-> UniProt:Q14511-2 (IntAct) [UndirectedInteraction:12284295] UniProt:P25963 <-> UniProt:Q96HA1-2 (IntAct) [UndirectedInteraction:12284293] UniProt:P25963 <-> UniProt:O43242 (IntAct) [UndirectedInteraction:12284291] UniProt:P25963 <-> UniProt:Q14511 (IntAct) [UndirectedInteraction:12284289] UniProt:P25963 <-> UniProt:Q04206-2 (IntAct) [UndirectedInteraction:12284285] UniProt:P25963 <-> UniProt:Q9UKB1 (IntAct) [UndirectedInteraction:12284283] UniProt:P25963 <-> UniProt:Q01201 (IntAct) [UndirectedInteraction:12284281] UniProt:P25963 <-> UniProt:Q9Y297 (IntAct) [UndirectedInteraction:12284279] UniProt:P25963 <-> UniProt:P35221 (IntAct) [UndirectedInteraction:12284277] UniProt:P25963 <-> UniProt:Q8N668 (IntAct) [UndirectedInteraction:12284275] UniProt:P25963 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12284275] UniProt:P25963 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12284273] UniProt:P25963 <-> UniProt:Q9J0X9 (IntAct) [UndirectedInteraction:12284271] UniProt:P25963 <-> UniProt:P21530-PRO_0000038062 (IntAct) [UndirectedInteraction:12284269] UniProt:P25963 <-> UniProt:Q04206-1 (IntAct) [UndirectedInteraction:12284267] UniProt:P25963 <-> UniProt:Q04864 (IntAct) [UndirectedInteraction:12284265] UniProt:P25963 <-> UniProt:P23396 (IntAct) [UndirectedInteraction:12284263] UniProt:P25963 <-> IntAct:EBI-10826665 (IntAct) [UndirectedInteraction:12284259] UniProt:P25963 <-> IntAct:EBI-4399559 (IntAct) [UndirectedInteraction:12284257] UniProt:P25963 <-> UniProt:Q9NWT6 (IntAct) [UndirectedInteraction:12284255] UniProt:P25963 <-> UniProt:P19838 (IntAct) [UndirectedInteraction:12284253] UniProt:P25963 <-> UniProt:Q04206 (IntAct) [UndirectedInteraction:12269497] UniProt:O00411 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12269361] UniProt:P27986 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12268759] UniProt:O14920 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12262757] UniProt:P25098 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12251335] UniProt:O15111 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12224667] UniProt:P34947 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12217141] UniProt:Q9Y6K9 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12216221] UniProt:Q04207 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12209119] UniProt:Q00653 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:12204587] UniProt:P0CG48 <-> UniProt:P25963 (IntAct)

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